The chemotherapeutic potential of polyamine antimetabolites

The polyamines, putrescine, spermidine and spermine are small cationic molecules essential for DNA synthesis and cell replication. Because the cytotoxicity of most anti-cancer drugs can be attributed to inhibitory effects on DNA synthesis and cell replication it led to speculation that inhibition of polyamine synthesis could be a useful tool in the control of neoplastic growth. In 1978 alpha-difluoromethylornithine (DFMO), a powerful inhibitor of ornithine decarboxylase, the rate limiting enzyme in polyamine synthesis, was synthesized by Metcalf. Since then numerous investigators have tested the potential of DFMO and other polyamine antimetabolites as chemotherapeutic agents in experimental animals and cell cultures. The accumulated knowledge is now being evaluated in the treatment of human proliferative disorders and cancer.